Antibodies as tools in cancer treatment

The Medical Biotechnology and Immunotherapy research group, led by Professor Stefan Barth, was launched in this year.

The rising incidence of cancer in Africa coupled with the spiralling prices of leading therapies indicates that there is a great need for locally developed immune-oncology diagnostics and therapeutics.

Following 20 years of work in the fields of medical biotechnology and immunotherapy in Germany, Professor Stefan Barth was recruited by the Department of Science and Technology/National Research Foundation’s South African Research Chair (SARChI) in 2015 to lead the Tier 1 Chair in Cancer Biotechnology at UCT. Bringing significant experience in the development and translation of immuno-diagnostics and immunotherapeutics, Barth has been tasked with establishing the first medical biotechnology-based immunotherapy laboratory in the country.

Barth is a prolific inventor with 35 patents filed prior to his arrival at UCT (22 of which have been granted, mainly in the United States and European Union up to now). Since joining UCT, he has filed – or is in the process of filing – three further patents that Research Contracts & Innovation (RC&I) are assisting him with.

The laboratory officially started operations in July 2016 staffed with two postdoctoral fellows, two PhD students and five honours students. Since then, it has received several awards and continues to develop programmes connecting its technologies to local and international researchers.

Joining the rising tide of research around more targeted approaches to cancer diagnosis and treatment, Barth and his group are specifically interested in using antibodies as both diagnostic and therapeutic tools.

Following a recent expansion of the team to 24 members in 2017, the Medical Biotechnology and Immunotherapy (MB&I) research group was launched in 2018, and received a five-year accreditation as a university-recognised unit. Barth has been closely assisted from the start by Dr Shivan Chetty, who also heads up research strategy and innovation for MB&I.

Harnessing antibodies as diagnostic tools

Joining the rising tide of research around more targeted approaches to cancer diagnosis and treatment, Barth and his group are specifically interested in using antibodies as both diagnostic and therapeutic tools.

Following a recent expansion of the team to 24 members in 2017, the Medical Biotechnology and Immunotherapy (MB&I) research group was launched in 2018, and received a five-year accreditation as a university-recognised unit.

The challenge to this approach lies in identifying the correct antibodies and tracking them successfully. “Human beings produce antibodies as one line of defence and these antibodies bind to specific pathogens as part of the immune system’s job to remove them from the body,” explains Barth. In practice, this means that antibodies are raised against virtually any foreign antigen and can be used to specifically detect, for instance, a tumour cell.

With regards to the challenge of identifying antibodies, Barth states that “the specificity of an antibody is confirmed by whether it binds only to tumour cells or also to surrounding normal cells”. Once this has been established, the antibodies that bind only to the tumour cells are collected and further validated for their diagnostic and therapeutic potential.

As for the second component of successfully tracking the antibodies, Barth continues that “once you have these antibodies, you would need to attach a label that would confirm binding of the antibody to the tumour cell.

“So, if you attach a fluorescent label, you would be able to see it using confocal microscopy on tissue sections from cancer patients. If it’s a radio label, you would be able to see it using radioimaging of the patient.”

Turning these diagnostic tools into therapeutic solutions

Once an antibody has been used successfully as a diagnostic tool by binding to tumour cells only, the very same antibody can be used to deliver a therapeutic substance directly to these cells. To do this, an appropriate therapeutic label would need to be attached to the antibody. In photodynamic therapy applications, for example, the diagnostic label is replaced by a label with both imaging and therapeutic activities. As soon as accumulation of the antibody has been confirmed at a tumour lesion by diagnostic imaging, the clinician can activate the therapeutic part of the antibody by introducing light on demand.

Once an antibody has been used successfully as a diagnostic tool by binding to tumour cells only, the very same antibody can be used to deliver a therapeutic substance directly to these cells.

Taking this one step further, MB&I are also looking at the ways antibodies can be used to discriminate between different stages of disease. This would allow clinicians to recognise which therapeutic label will be most appropriate for a specific patient and then selectively attach this label to the antibody responsible for detecting the disease stage. This facilitates more efficient treatments, as damage to normal, healthy cells is reduced while also eliminating therapies with little to no benefits to the patient.

Funding and partnerships

The team will seek to commercialise the group’s portfolio of patents through CURIT Biotechnology, a South African company founded by Barth and Dries Oelofse. Oelofse has co-developed the CURIT business plan and is engaged in company fund-raising initiatives. RC&I is supporting CURIT to provide access to the ‘pipeline’ of intellectual property (IP) that will pique potential investors’ interest. A further aim is that CURIT will provide local employment opportunities through separately funded subsidiaries for highly-skilled postgraduate students when they complete their studies.

MB&I are also looking at the ways antibodies can be used to discriminate between different stages of disease.

To refine the focus of the venture, RC&I has made use of National IP Management Office (NIPMO) funding to conduct a strategic review of Barth’s patent portfolio. Dr Ana Casanueva conducted an analysis to determine how the different intellectual property rights in the portfolio linked with one another and then arranged them into appropriate groupings that represented different commercial target products. Dr Casanueva has a technical qualification in biotechnology and experience in the technology transfer profession, so is familiar patents and the commercialisation of IP. This background enabled her to provide RC&I with a clear perspective of the key IP rights that will be essential to the success of the business.

Apart from CURIT, the group is supported by another start-up known as Nautilus Biosciences under the leadership of Chetty and co-founded by Barth. It aims to offer translational support for both the group’s work as well as other researchers in this environment.

UCT appreciates the support received from the Department of Science & Technology’s National Intellectual Property Management Office (NIPMO) for the up to 50% rebate on patenting costs incurred by the university, as well as funding that has enabled this case studies to be presented.